Enhancing Permeation of Drug Molecules Across the Skin via Delivery in Nanocarriers: Novel Strategies for Effective Transdermal Applications

Abstract

The transdermal route of administration provides numerous advantages over conventional routes i.e., oral or injectable for the treatment of different diseases and cosmetics applications. The skin also works as a reservoir, thus deliver the penetrated drug for more extended periods in a sustained manner. It reduces toxicity and local irritation due to multiple sites for absorption and owes the option of avoiding systemic side effects. However, the transdermal route of delivery for many drugs is limited since very few drugs can be delivered at a viable rate using this route. The stratum corneum of skin works as an effective barrier, limiting most drugs’ penetration posing difficulty to cross through the skin. Fortunately, some non-invasive methods can significantly enhance the penetration of drugs through this barrier. The use of nanocarriers for increasing the range of available drugs for the transdermal delivery has emerged as a valuable and exciting alternative. Both the lipophilic and hydrophilic drugs can be delivered via a range of nanocarriers through the stratum corneum with the possibility of having local or systemic effects to treat various diseases. In this review, the skin structure and major obstacle for transdermal drug delivery, different nanocarriers used for transdermal delivery, i.e., nanoparticles, ethosomes, dendrimers, liposomes, etc., have been discussed. Some recent examples of the combination of nanocarrier and physical methods, including iontophoresis, ultrasound, laser, and microneedles, have also been discussed for improving the therapeutic efficacy of transdermal drugs. Limitations and future perspectives of nanocarriers for transdermal drug delivery have been summarized at the end of this manuscript.

Topical Artocarpus communis Nanoparticles Improved the Water Solubility and Skin Permeation of Raw A. communis Extract, Improving Its Photoprotective Effect

“…It is well known that the stratum corneum is the most important skin barrier layer, affecting the skin absorption of many active ingredients and reducing their biological activities. Topical nanoparticle antioxidant formulations are one of the cutaneous delivery systems for enhancing the cutaneous absorption of antioxidants for preventing many skin problems [ 36 ]. Our results show that raw ACM could not only not penetrate the stratum corneum, but also was not deposited in the epidermis and dermis, indicating that the stratum corneum prevents ACM from being absorbed by the skin due to the poor water solubility of raw ACM ( Figure 5 ).…”

Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability

“…Nevertheless, there are many tasks to be solved, e.g., nanocarriers for transdermal delivery, and like any system they have their own drawbacks; so far, these include insufficiently overcoming the stratum corneum and the difficulty of achieving high drug concentrations to increase their therapeutic effect. In this case, a promising way is the combination of nanocarrier strategy and physical methods for improved drug delivery through the skin, for example, iontophoretic delivery, the use of ultrasound and microneedles [270,271]. In [272], the use of ethosomes in combination with sonoporation and electroporation improved transdermal delivery of calcein.…”

The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years

“…Current approaches encompass: (i) physical methods like sonophoresis, iontophoresis, thermophoresis, electroporation, laser microporation, thermal ablation, or microneedle patches [ 6 ]; (ii) encapsulation in suitable nanocarriers (nanoparticles, liposomes, ethosomes, niosomes, aquasomes, etc.) [ 7 ]; (iii) use of engineered controlled-release and/or stimuli-responsive materials (patches, wearable devices, and others) [ 8 ]; and (iv) addition of [bio]chemical permeation enhancers (e.g., fatty acids, fatty alcohols, alcohols, glycols, peptides, [bio]surfactants) [ 9 ]. Some of these methods can be combined, to further improve the percutaneous permeation efficiency.…”